Vaccines are effective means for combating infectious diseases. Depending on applicable people, vaccines can be divided into prophylactic vaccines and therapeutic vaccines. Prophylactic vaccines are mainly used to prevent virus infections, including attenuated vaccines, inactivated vaccines, and genetically engineering vaccines, which protect organisms from virus infections mainly by inducing neutralizing antibodies in the organisms. Therapeutic vaccines are mainly used to treat persistent virus infection and diseases such as tumor. In these diseases, patients are generally immune-tolerant to a target antigen, and therefore, researchers have tried several forms of vaccines to induce generation of an effective immune response to a target antigen in organisms. Therapeutic vaccines mainly include nucleic acid vaccines, viral vector vaccines, genetically engineering vaccines, etc. Among them, genetically engineering vaccines have significant advantages.
The genetically engineering vaccines that have been commercially available, include hepatitis B virus (HBV) vaccines, Human Papillomavirus (HPV) vaccines, and Hepatitis E virus (HEV) vaccines, all of which are in the form of virus-like particles (VLPs). Virus-like particles refer to hollow particles formed by one or more structural proteins of a certain virus, which do not comprise viral nucleic acid, cannot be self-replicated, but are the same as or similar to true virions in terms of morphology and structure. Virus-like particles have the following advantages: strong immunogenicity, high safety, being not easily inactivated, and being able to present an exogenous peptide fragment and induce specific immune response to the exogenous peptide fragment in organisms; and therefore, have an important application value in the field of vaccines.
Now, about 2 billion people have been infected by HBV worldwide, about 350 million of which have chronic HBV infection, and the risk of these infected people finally dying of liver diseases associated with HBV infection could reach 15%-25%. More than 1 million people died of end-stage liver diseases caused by hepatitis B worldwide every year. China is an area severely afflicted by HBV infection, and there are about 93 million people carrying hepatitis B now. In recent years, with the continuous improvement of the case reporting system, the incidence and mortality of hepatitis B-related diseases increase instead of decreasing.
At present, drugs for treating chronic HBV infection can mainly be divided into two classes, i.e., Interferon and nucleoside/nucleotide analogues (NAs). The final goal of treating chronic HBV infection is to prevent the occurrence of end-stage liver diseases such as serious hepatitis (hepatic failure), hepatic cirrhosis and liver cancer; the best clinical endpoint is to enable patients to achieve serological negative conversion or serological conversion of hepatitis B surface antigen, i.e., completely clean HBV. However, there are a very limited number of existing drugs that can achieve the goal. Therefore, it is urgent and necessary to develop novel, creative therapeutic drugs and methods that can clean virus more effectively, in particular, can clean HBsAg effectively or greatly decrease HBsAg level, for patients with chronic HBV infection, and it is a potential strategy to develop therapeutic vaccines.